Extracellular Vesicles Derived from Neural Progenitor Cells––a Preclinical Evaluation for Stroke Treatment in Mice

2020 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Extracellular Vesicles Derived from Neural Progenitor Cells––a Preclinical Evaluation for Stroke Treatment in Mice​
Zheng, X.; Zhang, L.; Kuang, Y.; Venkataramani, V. ; Jin, F.; Hein, K. & Zafeiriou, M. P.  et al.​ (2020) 
Translational Stroke Research12(1) pp. 185​-203​.​ DOI: https://doi.org/10.1007/s12975-020-00814-z 

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Authors
Zheng, X.; Zhang, L.; Kuang, Y.; Venkataramani, V. ; Jin, F.; Hein, K.; Zafeiriou, M. P. ; Lenz, C. ; Möbius, Wiebke ; Kilic, E. ; Hermann, D. M.; Urlaub, H. ; Zimmermann, W.-H. ; Bähr, M. ; Doeppner, Thorsten R. ; Weber, M. S.
Abstract
Stem cells such as mesenchymal stem cells (MSCs) enhance neurological recovery in preclinical stroke models by secreting extracellular vesicles (EVs). Since previous reports have focused on the application of MSC-EVs only, the role of the most suitable host cell for EV enrichment and preclinical stroke treatment remains elusive. The present study aimed to evaluate the therapeutic potential of EVs derived from neural progenitor cells (NPCs) following experimental stroke. Using the PEG technique, EVs were enriched and characterized by electron microscopy, proteomics, rt-PCR, nanosight tracking analysis, and Western blotting. Different dosages of NPC-EVs displaying a characteristic profile in size, shape, cargo protein, and non-coding RNA contents were incubated in the presence of cerebral organoids exposed to oxygen-glucose deprivation (OGD), significantly reducing cell injury when compared with control organoids. Systemic administration of NPC-EVs in male C57BL6 mice following experimental ischemia enhanced neurological recovery and neuroregeneration for as long as 3 months. Interestingly, the therapeutic impact of such NPC-EVs was found to be not inferior to MSC-EVs. Flow cytometric analyses of blood and brain samples 7 days post-stroke demonstrated increased blood concentrations of B and T lymphocytes after NPC-EV delivery, without affecting cerebral cell counts. Likewise, a biodistribution analysis after systemic delivery of NPC-EVs revealed the majority of NPC-EVs to be found in extracranial organs such as the liver and the lung. This proof-of-concept study supports the idea of EVs being a general concept of stem cell–induced neuroprotection under stroke conditions, where EVs contribute to reverting the peripheral post-stroke immunosuppression.
Issue Date
2020
Journal
Translational Stroke Research 
Project
EXC 2067: Multiscale Bioimaging 
SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz 
SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien 
SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle 
Working Group
RG Bähr (Neurobiological Research Laboratory) 
RG Möbius 
RG Zafeiriou (3D Electrically Excitable Cell Networks – Brain and Heart) 
RG Zimmermann (Engineered Human Myocardium) 
RG Lenz 
ISSN
1868-4483
eISSN
1868-601X
Language
English
Sponsor
TÜBITAK
Deutsche Forschungsgemeinschaft (DE)
German Center for Cardiovascular Research (DZHK)
Fondation Leducq

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